The toxicity of the anesthetic fluroxene (2,2,2-trifluoroethyl vinyl ether) and its analogues is mediated by hepatic microsomal cytochrome P-450. The in vitro metabolism of fluroxene by variously induced microsomal cytochromes P-450 will be studied and the results correlated with the effects of the inducing agents in potentiating the toxicity of fluroxene. Similar studies will be performed with analogues of fluroxene including fully saturated and epoxidized molecules. The effects of various inhibitors of cytochrome P-450 on the rates of in vitro microsomal metabolism of fluroxene and on the toxicity of fluroxene in induced rats will be tested. The ability of a series of substituted barbiturates to potentiate the toxicity of fluroxene will be studied and the results correlated with the hepatic mixed function oxidase inducing properties of the barbiturates and their physicochemical properties. The results of these studies will be utilized to gain understanding of the toxicity of fluroxene including its lethal effects, hepatotoxicity and destruction of cytochrome P-450.